1. Field of the Invention
The compositions and methods provided herein relate generally to therapeutic compositions that include extracts derived from Nerium species and methods of treatment using the compositions.
2. Description of the Related Art
Glutathione (GSH) is a tripeptide synthesized by the liver from three amino acids: glutamic acid, cysteine and glycine. The tripeptide contains an unusual peptide linkage between the amine group of cysteine and the carboxyl group of the glutamate side chain. Because it is synthesized in the body, glutathione is not considered an essential nutrient. However, in cases of increased exposure to toxic substances or reactive oxygen species, as is often the case in disease states, its rate of synthesis may be lower than the rate of turnover, in which case glutathione becomes a “conditionally essential nutrient”. Diet can contribute significant amounts of glutathione, which can be reasonably well absorbed in the intact state and is resistant to digestion because of the atypical nature of the amino acid bonds in the peptide (as compared to those typically found in dietary protein).
Glutathione, an antioxidant, protects cells from toxic substances such as free radicals (e.g. reactive oxygen species) and has been shown to prevent cancer development in animal models. Low dietary glutathione has been associated with increased incidence of oral and pharyngeal cancer. The administration of N-acetylcysteine has been reported to increase glutathione levels and to help reduce chemically induced lung tumors in animals. In response to increased interest in glutathione as a cancer preventive/resistive substance, the National Cancer Institute has been compiling data on the glutathione content of foods. The function of glutathione as a nutrient having cancer preventive properties, and its relationship to diet and detoxification activity, continue to be a rich research area which may provide new opportunities for preventing or treating cancer and other diseases.
The term “oleander” refers to two plant species, Nerium oleander (common oleander) and Thevetia peruviana (yellow oleander) which grow in temperate climates throughout the world. Both species contain chemicals called cardiac glycosides which have effects similar to the heart drug digoxin and can be toxic when taken by mouth, with many documented reports of deaths. It is estimated that as many as 100 chemical substances are present in various parts of the oleander plant. Laboratory studies of oleander suggest possible anti-cancer effects, although reliable research in humans has not yet been performed. There are also reports that long-term use of oleander may have positive effects in patients with leiomyosarcoma, Ewings's sarcoma, prostate or breast cancer. Oleander has also been used for other medicinal purposes including itchiness relief, hair loss prevention, syphilis treatment, as a gargle to strengthen teeth and gums, and as a nose drop for children.
Nerium oleander (N. oleander) is a common ornamental evergreen shrub which is used as a freeway median divider in warmer states such as California. This plant is extremely toxic and a single leaf may kill an adult. The toxicity of N. oleander is derived primarily from the presence of the cardiac glycoside oleandrin. Nerium oleander leaf extracts have recently completed Phase 1 clinical evaluation as a potential treatment for cancer.
Non-toxic, water-soluble extracts of N. oleander have been used in the treatment of various cancers and dementias, and also to boost the immune system in healthy subjects as described in U.S. Pat. No. 5,135,745 and U.S. Pat. No. 6,565,897 which are incorporated herein by reference in their entirety. The characterization of the biological activity of the extracts suggested that their activity potentiates an immune response by modulating the effects of cells in the immune system. The water-soluble extracts contained, among other ingredients, one or more immunologically active polysaccharides which may be useful in treating cell-proliferative disease in mammals. The results of such treatments have suggested that Nerium species extracts may be useful as non-toxic therapeutic agents to treat a variety of diseases or disorders including malignant and non-malignant cell proliferative diseases and disorders, infectious diseases, immune deficient diseases, dementias and pain. However, although the therapeutic use of such extracts has ameliorated or suppressed diseases in many patients, it has proven difficult to get a consistent response to the extracts in most or all patients and some patients did not respond at all.
Although methods for providing extracts of Nerium species have been disclosed which do not require a polar inorganic solvent such as water in the extraction process, those approaches suffer from the disadvantage that the alternative technologies and processes used can reduce or alter the amount, number, type, or activity of therapeutically beneficial components in the extract, including immunologically active polysaccharides. The therapeutic potential of such extracts can therefore be highly dependent upon the particular compounds retained therein as a result of the nature of the extraction process.
What is needed therefore are non-toxic Nerium species extracts and which, either alone or in conjunction with other agents or compounds, can provide clinically useful and consistent therapeutic benefits, preferably for a wide variety of diseases at relatively low concentrations.